TSC1 - Wiki-MPM

Interactant Symbol	Name	Associated Pathways Hide	Binding Drugs Hide	Associated Diseases Hide
YWHAE	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon	Activation of BAD and translocation to mitochondria Translocation of SLC2A4 (GLUT4) to the plasma membrane Signaling by Hippo NADE modulates death signalling Regulation of PLK1 Activity at G2/M Transition Regulation of HSF1-mediated heat shock response HSF1 activation Loss of Nlp from mitotic centrosomes Recruitment of mitotic centrosome proteins and complexes Loss of proteins required for interphase microtubule organization from the centrosome Recruitment of NuMA to mitotic centrosomes Anchoring of the basal body to the plasma membrane RHO GTPases activate PKNs TP53 Regulates Metabolic Genes Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex AURKA Activation by TPX2 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models RAB GEFs exchange GTP for GDP on RABs	Fusicoccin Phenethyl Isothiocyanate	Lissencephaly (LIS); Miller-Dieker syndrome (MDLS)
KAT2A	lysine acetyltransferase 2A	Pre-NOTCH Transcription and Translation Pre-NOTCH Transcription and Translation Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells NOTCH1 Intracellular Domain Regulates Transcription NOTCH1 Intracellular Domain Regulates Transcription Constitutive Signaling by NOTCH1 PEST Domain Mutants Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants HATs acetylate histones Notch-HLH transcription pathway B-WICH complex positively regulates rRNA expression Ub-specific processing proteases RNA Polymerase I Transcription Initiation RUNX3 regulates NOTCH signaling RUNX3 regulates NOTCH signaling NOTCH3 Intracellular Domain Regulates Transcription NOTCH3 Intracellular Domain Regulates Transcription NOTCH4 Intracellular Domain Regulates Transcription	Coenzyme A
MYC	MYC proto-oncogene, bHLH transcription factor	Transcription of E2F targets under negative control by DREAM complex NOTCH1 Intracellular Domain Regulates Transcription SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription Constitutive Signaling by NOTCH1 PEST Domain Mutants Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants Binding of TCF/LEF:CTNNB1 to target gene promoters MAPK6/MAPK4 signaling Ub-specific processing proteases Interleukin-4 and Interleukin-13 signaling Cyclin E associated events during G1/S transition Cyclin A:Cdk2-associated events at S phase entry TFAP2 (AP-2) family regulates transcription of cell cycle factors RUNX3 regulates WNT signaling Estrogen-dependent gene expression Transcriptional regulation of granulopoiesis	Acetylsalicylic acid Nadroparin	Choriocarcinoma Penile cancer Burkitt lymphoma Oral cancer Acute lymphoblastic leukemia (ALL) (precursor T lymphoblastic leukemia) Multiple myeloma Small cell lung cancer Acute lymphoblastic leukemia (ALL) (precursor B lymphoblastic leukemia) Osteosarcoma Kaposi's sarcoma Laryngeal cancer Breast cancer Ovarian cancer
CCNE1	cyclin E1	G0 and Early G1 SCF(Skp2)-mediated degradation of p27/p21 DNA Damage/Telomere Stress Induced Senescence Association of TriC/CCT with target proteins during biosynthesis TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest CDK-mediated phosphorylation and removal of Cdc6 Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes Cyclin E associated events during G1/S transition G1/S-Specific Transcription Cyclin D associated events in G1 p53-Dependent G1 DNA Damage Response PTK6 Regulates Cell Cycle Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) RHOBTB3 ATPase cycle		Laryngeal cancer Gastric cancer
FGFR4	fibroblast growth factor receptor 4	PI3K Cascade PIP3 activates AKT signaling betaKlotho-mediated ligand binding FGFR4 mutant receptor activation FGFR4 ligand binding and activation Constitutive Signaling by Aberrant PI3K in Cancer Phospholipase C-mediated cascade; FGFR4 FRS-mediated FGFR4 signaling SHC-mediated cascade:FGFR4 PI-3K cascade:FGFR4 Negative regulation of FGFR4 signaling Signaling by FGFR4 in disease RAF/MAP kinase cascade PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	Heparin Ponatinib Lenvatinib Erdafitinib Pemigatinib
YWHAG	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma	Activation of BAD and translocation to mitochondria Translocation of SLC2A4 (GLUT4) to the plasma membrane Regulation of PLK1 Activity at G2/M Transition Loss of Nlp from mitotic centrosomes Recruitment of mitotic centrosome proteins and complexes Loss of proteins required for interphase microtubule organization from the centrosome Recruitment of NuMA to mitotic centrosomes Anchoring of the basal body to the plasma membrane RHO GTPases activate PKNs TP53 Regulates Metabolic Genes Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex AURKA Activation by TPX2 Regulation of localization of FOXO transcription factors
YWHAZ	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta	Activation of BAD and translocation to mitochondria Translocation of SLC2A4 (GLUT4) to the plasma membrane Deactivation of the beta-catenin transactivating complex Rap1 signalling GP1b-IX-V activation signalling KSRP (KHSRP) binds and destabilizes mRNA Interleukin-3, Interleukin-5 and GM-CSF signaling RHO GTPases activate PKNs TP53 Regulates Metabolic Genes Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex NOTCH4 Activation and Transmission of Signal to the Nucleus Negative regulation of NOTCH4 signaling Regulation of localization of FOXO transcription factors	Phenethyl Isothiocyanate
TCF7L2	transcription factor 7 like 2	Formation of the beta-catenin:TCF transactivating complex Formation of the beta-catenin:TCF transactivating complex Deactivation of the beta-catenin transactivating complex Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) Ca2+ pathway Binding of TCF/LEF:CTNNB1 to target gene promoters Repression of WNT target genes Repression of WNT target genes Signaling by TCF7L2 mutants Transcriptional Regulation by VENTX RUNX3 regulates WNT signaling		Type II diabetes mellitus
ARAF	A-Raf proto-oncogene, serine/threonine kinase	RAF activation MAP2K and MAPK activation Negative regulation of MAPK pathway Signaling by moderate kinase activity BRAF mutants Signaling by high-kinase activity BRAF mutants Signaling by BRAF and RAF fusions Paradoxical activation of RAF signaling by kinase inactive BRAF Signaling downstream of RAS mutants Signaling by RAF1 mutants Signaling by MRAS-complex mutants	ATP	Noonan syndrome and related disorders, including: Noonan syndrome (NS); Leopard syndrome (LS); Noonan syndrome-like with loose anagen hair (NS/LAH); CBL-mutation associated syndrome (CBL); Neurofibromatosis type 1 (NF1); Neurofibromatosis type 2 (NF2); Neurofibromatosis-Noonan syndrome (NFNS); Legius syndrome; Cardiofaciocutaneous syndrome (CFCS); Costello syndrome (CS)
AURKA	aurora kinase A	APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 Regulation of PLK1 Activity at G2/M Transition SUMOylation of DNA replication proteins TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest Regulation of TP53 Activity through Phosphorylation FBXL7 down-regulates AURKA during mitotic entry and in early mitosis AURKA Activation by TPX2 Interaction between PHLDA1 and AURKA	Phosphonothreonine AT9283 CYC116 Alisertib SNS-314 Cenisertib Enzastaurin 4-(4-METHYLPIPERAZIN-1-YL)-N-[5-(2-THIENYLACETYL)-1,5-DIHYDROPYRROLO[3,4-C]PYRAZOL-3-YL]BENZAMIDE AKI-001 1-{5-[2-(thieno[3,2-d]pyrimidin-4-ylamino)ethyl]-1,3-thiazol-2-yl}-3-[3-(trifluoromethyl)phenyl]urea 1-(5-{2-[(1-methyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)amino]ethyl}-1,3-thiazol-2-yl)-3-[3-(trifluoromethyl)phenyl]urea N-{3-[(4-{[3-(TRIFLUOROMETHYL)PHENYL]AMINO}PYRIMIDIN-2-YL)AMINO]PHENYL}CYCLOPROPANECARBOXAMIDE N-butyl-3-{[6-(9H-purin-6-ylamino)hexanoyl]amino}benzamide 2-(1H-pyrazol-3-yl)-1H-benzimidazole N-[3-(1H-BENZIMIDAZOL-2-YL)-1H-PYRAZOL-4-YL]BENZAMIDE Fostamatinib MLN8054
CDK6	cyclin dependent kinase 6	Oxidative Stress Induced Senescence Senescence-Associated Secretory Phenotype (SASP) Oncogene Induced Senescence Cyclin D associated events in G1 Regulation of RUNX1 Expression and Activity Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6 Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	Alvocidib (2S)-2-({6-[(3-Amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methyl-1-butanol Fisetin Palbociclib Ribociclib Abemaciclib
KDM1A	lysine demethylase 1A	HDACs deacetylate histones HDMs demethylate histones Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 Regulation of PTEN gene transcription Estrogen-dependent gene expression NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux Potential therapeutics for SARS Factors involved in megakaryocyte development and platelet production
NEFL	neurofilament light	Unblocking of NMDA receptors, glutamate binding and activation Unblocking of NMDA receptors, glutamate binding and activation Ras activation upon Ca2+ influx through NMDA receptor RAF/MAP kinase cascade Assembly and cell surface presentation of NMDA receptors Negative regulation of NMDA receptor-mediated neuronal transmission Long-term potentiation		Charcot-Marie-Tooth disease (CMT); Hereditary motor and sensory neuropathy; Peroneal muscular atrophy
RHEB	Ras homolog, mTORC1 binding	Macroautophagy MTOR signalling mTORC1-mediated signalling Energy dependent regulation of mTOR by LKB1-AMPK TP53 Regulates Metabolic Genes Regulation of PTEN gene transcription Amino acids regulate mTORC1	Guanosine-5'-Triphosphate Guanosine-5'-Diphosphate
TSC2	TSC complex subunit 2	Macroautophagy Inhibition of TSC complex formation by PKB AKT phosphorylates targets in the cytosol Energy dependent regulation of mTOR by LKB1-AMPK TP53 Regulates Metabolic Genes Constitutive Signaling by AKT1 E17K in Cancer TBC/RABGAPs		Lymphangioleiomyomatosis (LAM) Tuberous sclerosis complex (TSC); Bourneville-Pringle disease
FRS3	fibroblast growth factor receptor substrate 3	FRS-mediated FGFR1 signaling FRS-mediated FGFR2 signaling FRS-mediated FGFR3 signaling FRS-mediated FGFR4 signaling RAF/MAP kinase cascade Activated NTRK2 signals through FRS2 and FRS3
YWHAQ	tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta	Activation of BAD and translocation to mitochondria Translocation of SLC2A4 (GLUT4) to the plasma membrane RHO GTPases activate PKNs TP53 Regulates Metabolic Genes Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex Regulation of localization of FOXO transcription factors	Phenethyl Isothiocyanate
CDKN2B	cyclin dependent kinase inhibitor 2B	SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription Oxidative Stress Induced Senescence Senescence-Associated Secretory Phenotype (SASP) Oncogene Induced Senescence Cyclin D associated events in G1		Malignant pleural mesothelioma Osteosarcoma Type II diabetes mellitus
CSTF2	cleavage stimulation factor subunit 2	tRNA processing in the nucleus mRNA Splicing - Major Pathway mRNA 3'-end processing RNA Polymerase II Transcription Termination Processing of Intronless Pre-mRNAs
VPS37C	VPS37C subunit of ESCRT-I	Budding and maturation of HIV virion Membrane binding and targetting of GAG proteins Endosomal Sorting Complex Required For Transport (ESCRT) HCMV Late Events Late endosomal microautophagy

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